Prevention of Reperfusion Injury Following Global Cardiac Ischemia

Background: The coronary endothelium produce endothelium-dependent relaxing factors (EDRF) for prevent vasospasm and thrombosis. However, with reperfusion after coronary ischemia, endothelium-dependent relaxation (EDR) is diminished due to G-protein dysfunction. Nitric oxide precursor or nitric oxide donor given before reperfusion would attenuate reperfusion injury. In this study, experiments will be designed to determine whether impaired coronary endothelium function could be improved by modification of cardioplegic solution after global cardiac ischemia and reperfusion. Methods and Results: Dogs were exposed to extracorporeal circulation and the body temperature was kept around 28.degree.C. The ascending aorta was cross-clamped for 60 minutes while intermittent cold crystalloid cardioplegic solution with (group 1 to 3) or without (group 4) supplement L-arginine, 3-morpholinosylnomimine (SIN-1), N/sup G/-nitro-1-arginine-methylester (L-NAME) respectively was infused into the aortic root. The heart was then allowed to function for another 60 minutes of reperfusion. Endothelium-derived relaxation in response to acetylcholine, adenosine diphosphate and sodium fluoride of coronary rings in group 1 and 3 were significantly different from that of group 2 and 4. In contrast, EDR in response to A23187 was significantly better in group 2 than in group 1 and group 3. Conclusions: These data suggests that canine coronary endothelium can reverse G-protein dysfunction by supplementation of L-arginine or SIN-1 in cold crystalloid cardioplegia and infusion it during global ischemia and reperfusion. However, this treatment can not improve receptor-independent, G-protein-independent EDR to A23187.

Project ID:PB8602-1023
External Project ID:NSC86-2314-B182-016